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Jaundice
CHAPTER
7
Jaundice I. INTRODUCTION Jaundice is an abnormal yellowish discoloration of the skin and mucous membranes caused by accumulation of bile pigment. There are three forms: (1) hemolytic jaundice (due to increased bilirubin production from excessive breakdown of red cells), (2) hepatocellular jaundice (due to disease of the liver parenchyma, e.g., alcoholic liver disease, drug-induced liver disease, viral hepatitis, or metastatic carcinoma), and (3) obstructive jaundice (due to mechanical obstruction of the biliary ducts outside the liver, e.g., choledocholithiasis or pancreatic carcinoma). In most published series of jaundiced patients, hemolysis is uncommon, and the usual task of the clinician at the bedside is to differentiate hepatocellular disease from obstructed biliary ducts.1,2
II. FINDINGS A. JAUNDICE Jaundice is usually first noted in the eyes, but the traditional term for this finding (scleral icterus) is actually a misnomer because pathologic studies reveal most of the pigment to be deposited in the conjunctiva, not the avascular sclera.3 As jaundice progresses and the serum bilirubin increases, the face, mucous membranes, and eventually the entire skin acquire a yellow or orange hue. Prominent yellowish subconjunctival fat may be mistaken for conjunctival jaundice, but fat usually is limited to the conjunctival folds and, unlike jaundice, spares the area near the cornea. Patients with carotenemia (from excess carrot or multivitamin ingestion) also develop a yellowish discoloration of the skin, especially the palms, soles, and nasolabial fold, but, in contrast to jaundice, the conjunctiva are spared.4 B. ASSOCIATED FINDINGS According to classic teachings, several findings distinguish hepatocellular disease from obstructed biliary ducts. 1. Hepatocellular Jaundice Characteristic findings are spider telangiectasias, palmar erythema, gynecomastia, dilated abdominal wall veins, splenomegaly, asterixis, and fetor hepaticus. 63
64 PART 3 — GENERAL APPEARANCE OF THE PATIENT
a. Spider Telangiectasias (Spider Angiomas) Spider telangiectasias are dilated cutaneous blood vessels with three components: (1) a central arteriole (the “body” of the spider) that when compressed slightly with a glass slide, can be seen to pulsate; (2) multiple radiating “legs”; and (3) surrounding erythema, which may encompass the entire lesion or only its central portion.5 After blanching, the returning blood fills the central arteriole first before traveling to the peripheral tips of each leg. Spiders are most numerous on the face and neck, followed by the shoulders, thorax, arms, and hands. They are rare on the palms and scalp and below the umbilicus.5 This peculiar distribution may reflect the neurohormonal properties of the microcirculation because it is similar to the distribution of blushing where it is most intense.5 Acquired vascular spiders are associated with three clinical conditions: liver disease, pregnancy, and malnutrition.6 In patients with liver disease, the spiders advance and regress with disease severity,7 and their appearance correlates somewhat with an abnormally increased ratio of serum estradiol to testosterone levels.8 In pregnant women, spiders typically appear between the second and fifth months and usually disappear within days after delivery.6 Vascular spiders also have been described in normal persons, but these lesions, in contrast to those of liver disease, are always few in number (average, three) and size.5 Vascular spiders were first described by the English physician Erasmus Wilson in 1867.5 b. Palmar Erythema Palmar erythema is a symmetrical reddening of the surfaces of the palms, most pronounced over the hypothenar and thenar eminences.6 Palmar erythema occurs in the same clinical conditions as vascular spiders, and the two lesions tend to come and go together.6 c. Gynecomastia and Diminished Body Hair Many patients with liver disease have gynecomastia (defined as a palpable, discrete button of firm subareolar breast tissue ≥2 cm in diameter) and diminished pubic and body hair; both findings are attributed to increased circulating estrogen-to-testosterone levels. d. Dilated Abdominal Veins In some patients with cirrhosis, elevated portal venous pressures lead to the development of collateral vessels from the portal venous to systemic venous systems. One group of such vessels surrounds the umbilicus, decompressing the left portal vein via the paraumbilical vessels into abdominal wall veins.9 Sometimes these abdominal wall veins become so conspicuous that they resemble a cluster of serpents, thus earning the name caput medusae.10 Collateral vessels may generate a continuous humming murmur heard during auscultation between the xiphoid and umbilicus.11 Collateral abdominal vessels also may appear in patients with superior vena cava syndrome (if the obstruction also involves the azygous system)12
CHAPTER 7 — JAUNDICE 65
or inferior vena cava syndrome.13 In these disorders, however, the vessels tend to appear on the lateral abdominal wall. A traditional test to distinguish inferior vena cava obstruction from portal hypertension is to strip abdominal wall veins below the umbilicus and see which way blood is flowing. (In portosystemic collaterals, blood should flow away from the umbilicus, whereas in inferior vena cava collaterals, flow is reversed and toward the head.) Even so, this test is unreliable because most dilated abdominal vessels lack competent valves, and the clinician can “demonstrate” that blood flows in either direction in most patients with both conditions. e. Palpable Spleen One of the principal causes of splenomegaly is portal hypertension from severe hepatocellular disease.14 Therefore, a traditional teaching is that the finding of splenomegaly in a jaundiced patient increases the probability of hepatocellular disease. f. Asterixis Originally described by Adams and Foley in 1949,15,16 asterixis is one of the earliest findings of hepatic encephalopathy and is thus a finding typical of hepatocellular jaundice. To elicit the sign, the patient holds both arms outstretched with fingers spread apart. After a short latent period, both fingers and hands commence to “flap,” with abrupt movements occurring at irregular intervals of a fraction of a second to seconds (thus earning the name liver flap). The fundamental problem in asterixis is the inability to maintain a fixed posture (the word asterixis comes from the Greek sterigma, meaning “to support”), and, consequently, asterixis can also be demonstrated by having the patient elevate the leg and dorsiflex the foot, close the eyelids forcibly, or protrude the tongue.15 Because some voluntary contraction of the muscles is necessary to elicit asterixis, the sign disappears once coma ensues (although some comatose patients exhibit the finding during the grasp reflex; see Chapter 61).15 Electromyography reveals that asterixis represents the abrupt disappearance of electrical activity in the muscle (i.e., negative myoclonus).17 Asterixis is not specific to liver disease but also appears in encephalopathy from other causes such as hypercapnia or uremia.18 Unilateral asterixis indicates structural disease in the contralateral brain.19,20 g. Fetor Hepaticus Fetor hepaticus is the characteristic breath of patients with severe parenchymal disease, which has been likened to a mixture of rotten eggs and garlic. Gas chromatography reveals that the principal compound causing the odor is dimethylsulfide.21 Fetor hepaticus correlates best with severe portosystemic shunting, not encephalopathy per se, because even alert patients with severe portosystemic shunting have the characteristic breath.22 2. Obstructive Jaundice: Palpable Gallbladder (Courvoisier Sign) The presence of a smooth, nontender, distended gallbladder in a patient with jaundice is a traditional sign of obstructive jaundice. Courvoisier
66 PART 3 — GENERAL APPEARANCE OF THE PATIENT
sign refers to the association of the palpable gallbladder and extrahepatic obstruction, a sign discussed fully in Chapter 49.
III. CLINICAL SIGNIFICANCE A. DETECTION OF JAUNDICE Although many textbooks claim that jaundice becomes evident once the serum bilirubin exceeds 2.5 to 3 mg/dL, clinical studies reveal that only 70% to 80% of observers detect jaundice at this threshold.23,24 The sensitivity of examination increases to 83% when bilirubin exceeds 10 mg/dL and 96% when it exceeds 15 mg/dL. B. HEPATOCELLULAR VERSUS OBSTRUCTIVE JAUNDICE Studies show that clinicians accurately distinguish hepatocellular jaundice from obstructive jaundice more than 80% of the time by just using bedside and basic laboratory findings (i.e., before clinical imaging).25,26 In EBM Box 7-1, disease is arbitrarily defined as hepatocellular disease: therefore, likelihood ratios (LRs) with large positive values increase the probability of hepatocellular disease, whereas those with values close to zero decrease it and thus increase probability for obstructive disease. These studies show that in patients presenting with jaundice, the physical signs of portal hypertension (dilated abdominal veins, LR = 17.5; ascites, LR = 4.4; and palpable spleen, LR = 2.9), palmar erythema (LR = 9.8), and spider angiomas (LR = 4.7) all increase the probability of hepatocellular jaundice. The only finding arguing strongly against hepatocellular jaundice is the palpable gallbladder (LR = 0.04; in other words, the finding of a palpable gallbladder argues for obstructed bile ducts with an LR of 26, the inverse of 0.04). Weight loss does not discriminate well between hepatocellular and obstructive causes. Also unhelpful are liver tenderness and a palpable liver. The palpable liver remains unhelpful even when it is defined as a liver edge extending more than four to five fingerbreadths below the right costal margin.25 C. DIAGNOSIS OF CIRRHOSIS The diagnosis of cirrhosis in patients with liver disease has important prognostic and therapeutic implications. EBM Box 7-2 displays the diagnostic accuracy of physical findings in detecting cirrhosis, determined from hundreds of patients presenting with diverse chronic liver diseases. According to this EBM box, the findings increasing the probability of cirrhosis the most are dilated abdominal wall veins (LR = 9.5), encephalopathy (irrational behavior, disordered consciousness, and asterixis; LR = 8.8), reduced body or pubic hair (LR = 8.8), gynecomastia (LR = 7), ascites (LR = 6.6), spider angiomas (LR = 4.5), palmar erythema (LR = 4.3), jaundice (LR = 3.8), and peripheral edema (LR = 3). Other findings (but less compelling ones) are a liver edge that is firm to palpation (LR = 2.7), a palpable left lobe of the liver in the epigastrium (LR = 2.7), and splenomegaly (LR = 2.5). The only findings decreasing the probability of cirrhosis in these patients are absence of a palpable liver in the epigastrium (LR = 0.3) and absence of a firm liver edge (LR = 0.4).
CHAPTER 7 — JAUNDICE 67
EBM BOX 7-1
Findings Predicting Hepatocellular Disease in Patients with Jaundice* Finding (Reference)†
Sensitivity (%)
Specificity (%)
General Appearance Weight loss25,27
10-49
Skin Spider angiomas25,27 Palmar erythema25 Dilated abdominal veins25 abdomen
Ascites25 Palpable spleen25,27 Palpable gallbladder25 Palpable liver25,27 Liver tenderness25,27
Likelihood Ratio‡ if Finding Is Present
Absent
21-97
NS
NS
35-47 49 42
88-97 95 98
4.7 9.8 17.5
0.6 0.5 0.6
44 29-47 0† 71-83 37-38
90 83-90 69 15-17 70-78
4.4 2.9 0.04 NS NS
0.6 0.7 1.4 NS NS
*Diagnostic standard: For nonobstructive (vs. obstructive) jaundice, needle biopsy of liver, surgical exploration, or autopsy. †None of the 41 patients with medical jaundice in this study had a palpable gallbladder; for calculation of the LRs, 0.5 was added to all cells of the 2×2 table. ‡Likelihood ratio (LR) if finding present = positive LR; LR if finding absent = negative LR. NS, not significant. Click here to access calculator. HEPATOCELLULAR JAUNDICE Probability Decrease Increase –45% –30% –15% +15% +30% +45% LRs
0.1
Palpable gallbladder
0.2
0.5
1
2
5
10
LRs
Dilated abdominal veins Palmar erythema Spider angiomata Ascites Palpable spleen
D. DETECTING LARGE GASTROESOPHAGEAL VARICES IN PATIENTS WITH CIRRHOSIS In studies of more than 700 patients with cirrhosis who have not had prior gastrointestinal bleeding, no physical finding reliably predicts which patients have significant gastroesophageal varices (as detected by endoscopy). For most findings—caput medusae, spider angiomas, jaundice, hepatomegaly, splenomegaly, and hepatic encephalopathy—the LR is not
68 PART 3 — GENERAL APPEARANCE OF THE PATIENT
EBM BOX 7-2
Findings Predicting Cirrhosis in Patients with Chronic Liver Disease* Finding (Reference)† Skin Spider angiomas6,28–38 Palmar erythema29,31,32,34,37 Gynecomastia29,37 Reduction of body or pubic hair29,37 Jaundice 29,33,35,37,39 Dilated abdominal wall veins29,34,37 Abdomen Hepatomegaly29,32–36,38,40 Palpable liver in epigastrium35,38 Liver edge firm to palpation32,40 Splenomegaly28,30–36,38–40 Ascites28,29,31,33–35,39
Sensitivity (%)
Specificity (%)
33-84 12-70
Present
Absent
48-98 49-98
4.5 4.3
0.5 0.6
18-58 24-51
92-97 94-97
7 8.8
NS NS
16-44 9-51
83-99 79-100
3.8 9.5
0.8 NS
31-96
20-96
2.3
0.6
50-86
68-88
2.7
0.3
71-78
71-74
2.7
0.4
35-100
2.5
0.8
14-52
82-99
6.6
0.8
24-56 9-29
87-92 98-99
3.0 8.8
0.7 NS
5-85
Other Findings Peripheral edema29,33,34 Encephalopathy28,29,31
Likelihood Ratio‡ if Finding Is
*Diagnostic standard: For cirrhosis, needle biopsy of liver. †Definition of findings: For hepatomegaly and splenomegaly, examining clinician’s impression using palpation, percussion, or both; encephalopathy, disordered consciousness and asterixis.15 ‡Likelihood ratio (LR) if finding present = positive LR; LR if finding absent = negative LR. NS, not significant. Click here to access calculator.
CIRRHOSIS Probability Decrease Increase – 45% –30% –15% +15% +30% +45% LRs
0.1
0.2
0.5
Liver not palpable in epigastrium Liver edge not firm to palpation
1
2
5
10
LRs
Dilated abdominal wall veins Encephalopathy Diminished body or pubic hair Gynecomastia Ascites Spider angiomata or palmar erythema
CHAPTER 7 — JAUNDICE 69
EBM BOX 7-3
Findings Detecting Hepatopulmonary Syndrome in Patients with Chronic Liver Disease* Finding (Reference)
Sensitivity (%)
Specificity (%)
Clubbing45–48 Cyanosis45,46 Palmar erythema45,49 Spider angiomas45–49 Ascites47,48
22-80 8-86 57-80 39-97 56-79
64-95 79-99 54-70 26-70 20-57
Likelihood Ratio† if Finding Is Present
Absent
4.6 4.3 NS 1.4 NS
0.6 NS NS NS NS
*Diagnostic standard: For hepatopulmonary syndrome, all three of the following criteria were present: (1) cirrhosis, (2) contrast echocardiography revealing intrapulmonary right→left shunting, and (3) hypoxemia, variably defined as arterial pO2 <70 mm Hg49 or <80 mm Hg,45 alveolar-arterial pO2 gradient ≥15 mm Hg48 or >20 mm Hg,46 or either pO2 <70 mm Hg or AapO2 >20 mm Hg.47 †Likelihood ratio (LR) if finding present = positive LR; LR if finding absent = negative LR. NS, not significant. Click here to access calculator. HEPATOPULMONARY SYNDROME Probability Decrease Increase –45% –30% –15% +15% +30% +45% LRs
0.1
0.2
0.5
1
2
5
10
LRs
Clubbing Cyanosis
significant; only for ascites is the LR statistically significant (LR = 1.5), although its clinical significance is minimal.41-44 E. DETECTING HEPATOPULMONARY SYNDROME Hepatopulmonary syndrome is a serious complication of cirrhosis causing intrapulmonary vascular shunting and significant hypoxemia. In five studies of over 400 patients with cirrhosis (EBM Box 7-3), most awaiting liver transplantation, the findings of finger clubbing (LR = 4.6) and cyanosis (LR = 4.3) increased the probability of hepatopulmonary syndrome. The references for this chapter can be found on www.expertconsult.com.
7
Jaundice I. INTRODUCTION Jaundice is an abnormal yellowish discoloration of the skin and mucous membranes caused by accumulation of bile pigment. There are three forms: (1) hemolytic jaundice (due to increased bilirubin production from excessive breakdown of red cells), (2) hepatocellular jaundice (due to disease of the liver parenchyma, e.g., alcoholic liver disease, drug-induced liver disease, viral hepatitis, or metastatic carcinoma), and (3) obstructive jaundice (due to mechanical obstruction of the biliary ducts outside the liver, e.g., choledocholithiasis or pancreatic carcinoma). In most published series of jaundiced patients, hemolysis is uncommon, and the usual task of the clinician at the bedside is to differentiate hepatocellular disease from obstructed biliary ducts.1,2
II. FINDINGS A. JAUNDICE Jaundice is usually first noted in the eyes, but the traditional term for this finding (scleral icterus) is actually a misnomer because pathologic studies reveal most of the pigment to be deposited in the conjunctiva, not the avascular sclera.3 As jaundice progresses and the serum bilirubin increases, the face, mucous membranes, and eventually the entire skin acquire a yellow or orange hue. Prominent yellowish subconjunctival fat may be mistaken for conjunctival jaundice, but fat usually is limited to the conjunctival folds and, unlike jaundice, spares the area near the cornea. Patients with carotenemia (from excess carrot or multivitamin ingestion) also develop a yellowish discoloration of the skin, especially the palms, soles, and nasolabial fold, but, in contrast to jaundice, the conjunctiva are spared.4 B. ASSOCIATED FINDINGS According to classic teachings, several findings distinguish hepatocellular disease from obstructed biliary ducts. 1. Hepatocellular Jaundice Characteristic findings are spider telangiectasias, palmar erythema, gynecomastia, dilated abdominal wall veins, splenomegaly, asterixis, and fetor hepaticus. 63
64 PART 3 — GENERAL APPEARANCE OF THE PATIENT
a. Spider Telangiectasias (Spider Angiomas) Spider telangiectasias are dilated cutaneous blood vessels with three components: (1) a central arteriole (the “body” of the spider) that when compressed slightly with a glass slide, can be seen to pulsate; (2) multiple radiating “legs”; and (3) surrounding erythema, which may encompass the entire lesion or only its central portion.5 After blanching, the returning blood fills the central arteriole first before traveling to the peripheral tips of each leg. Spiders are most numerous on the face and neck, followed by the shoulders, thorax, arms, and hands. They are rare on the palms and scalp and below the umbilicus.5 This peculiar distribution may reflect the neurohormonal properties of the microcirculation because it is similar to the distribution of blushing where it is most intense.5 Acquired vascular spiders are associated with three clinical conditions: liver disease, pregnancy, and malnutrition.6 In patients with liver disease, the spiders advance and regress with disease severity,7 and their appearance correlates somewhat with an abnormally increased ratio of serum estradiol to testosterone levels.8 In pregnant women, spiders typically appear between the second and fifth months and usually disappear within days after delivery.6 Vascular spiders also have been described in normal persons, but these lesions, in contrast to those of liver disease, are always few in number (average, three) and size.5 Vascular spiders were first described by the English physician Erasmus Wilson in 1867.5 b. Palmar Erythema Palmar erythema is a symmetrical reddening of the surfaces of the palms, most pronounced over the hypothenar and thenar eminences.6 Palmar erythema occurs in the same clinical conditions as vascular spiders, and the two lesions tend to come and go together.6 c. Gynecomastia and Diminished Body Hair Many patients with liver disease have gynecomastia (defined as a palpable, discrete button of firm subareolar breast tissue ≥2 cm in diameter) and diminished pubic and body hair; both findings are attributed to increased circulating estrogen-to-testosterone levels. d. Dilated Abdominal Veins In some patients with cirrhosis, elevated portal venous pressures lead to the development of collateral vessels from the portal venous to systemic venous systems. One group of such vessels surrounds the umbilicus, decompressing the left portal vein via the paraumbilical vessels into abdominal wall veins.9 Sometimes these abdominal wall veins become so conspicuous that they resemble a cluster of serpents, thus earning the name caput medusae.10 Collateral vessels may generate a continuous humming murmur heard during auscultation between the xiphoid and umbilicus.11 Collateral abdominal vessels also may appear in patients with superior vena cava syndrome (if the obstruction also involves the azygous system)12
CHAPTER 7 — JAUNDICE 65
or inferior vena cava syndrome.13 In these disorders, however, the vessels tend to appear on the lateral abdominal wall. A traditional test to distinguish inferior vena cava obstruction from portal hypertension is to strip abdominal wall veins below the umbilicus and see which way blood is flowing. (In portosystemic collaterals, blood should flow away from the umbilicus, whereas in inferior vena cava collaterals, flow is reversed and toward the head.) Even so, this test is unreliable because most dilated abdominal vessels lack competent valves, and the clinician can “demonstrate” that blood flows in either direction in most patients with both conditions. e. Palpable Spleen One of the principal causes of splenomegaly is portal hypertension from severe hepatocellular disease.14 Therefore, a traditional teaching is that the finding of splenomegaly in a jaundiced patient increases the probability of hepatocellular disease. f. Asterixis Originally described by Adams and Foley in 1949,15,16 asterixis is one of the earliest findings of hepatic encephalopathy and is thus a finding typical of hepatocellular jaundice. To elicit the sign, the patient holds both arms outstretched with fingers spread apart. After a short latent period, both fingers and hands commence to “flap,” with abrupt movements occurring at irregular intervals of a fraction of a second to seconds (thus earning the name liver flap). The fundamental problem in asterixis is the inability to maintain a fixed posture (the word asterixis comes from the Greek sterigma, meaning “to support”), and, consequently, asterixis can also be demonstrated by having the patient elevate the leg and dorsiflex the foot, close the eyelids forcibly, or protrude the tongue.15 Because some voluntary contraction of the muscles is necessary to elicit asterixis, the sign disappears once coma ensues (although some comatose patients exhibit the finding during the grasp reflex; see Chapter 61).15 Electromyography reveals that asterixis represents the abrupt disappearance of electrical activity in the muscle (i.e., negative myoclonus).17 Asterixis is not specific to liver disease but also appears in encephalopathy from other causes such as hypercapnia or uremia.18 Unilateral asterixis indicates structural disease in the contralateral brain.19,20 g. Fetor Hepaticus Fetor hepaticus is the characteristic breath of patients with severe parenchymal disease, which has been likened to a mixture of rotten eggs and garlic. Gas chromatography reveals that the principal compound causing the odor is dimethylsulfide.21 Fetor hepaticus correlates best with severe portosystemic shunting, not encephalopathy per se, because even alert patients with severe portosystemic shunting have the characteristic breath.22 2. Obstructive Jaundice: Palpable Gallbladder (Courvoisier Sign) The presence of a smooth, nontender, distended gallbladder in a patient with jaundice is a traditional sign of obstructive jaundice. Courvoisier
66 PART 3 — GENERAL APPEARANCE OF THE PATIENT
sign refers to the association of the palpable gallbladder and extrahepatic obstruction, a sign discussed fully in Chapter 49.
III. CLINICAL SIGNIFICANCE A. DETECTION OF JAUNDICE Although many textbooks claim that jaundice becomes evident once the serum bilirubin exceeds 2.5 to 3 mg/dL, clinical studies reveal that only 70% to 80% of observers detect jaundice at this threshold.23,24 The sensitivity of examination increases to 83% when bilirubin exceeds 10 mg/dL and 96% when it exceeds 15 mg/dL. B. HEPATOCELLULAR VERSUS OBSTRUCTIVE JAUNDICE Studies show that clinicians accurately distinguish hepatocellular jaundice from obstructive jaundice more than 80% of the time by just using bedside and basic laboratory findings (i.e., before clinical imaging).25,26 In EBM Box 7-1, disease is arbitrarily defined as hepatocellular disease: therefore, likelihood ratios (LRs) with large positive values increase the probability of hepatocellular disease, whereas those with values close to zero decrease it and thus increase probability for obstructive disease. These studies show that in patients presenting with jaundice, the physical signs of portal hypertension (dilated abdominal veins, LR = 17.5; ascites, LR = 4.4; and palpable spleen, LR = 2.9), palmar erythema (LR = 9.8), and spider angiomas (LR = 4.7) all increase the probability of hepatocellular jaundice. The only finding arguing strongly against hepatocellular jaundice is the palpable gallbladder (LR = 0.04; in other words, the finding of a palpable gallbladder argues for obstructed bile ducts with an LR of 26, the inverse of 0.04). Weight loss does not discriminate well between hepatocellular and obstructive causes. Also unhelpful are liver tenderness and a palpable liver. The palpable liver remains unhelpful even when it is defined as a liver edge extending more than four to five fingerbreadths below the right costal margin.25 C. DIAGNOSIS OF CIRRHOSIS The diagnosis of cirrhosis in patients with liver disease has important prognostic and therapeutic implications. EBM Box 7-2 displays the diagnostic accuracy of physical findings in detecting cirrhosis, determined from hundreds of patients presenting with diverse chronic liver diseases. According to this EBM box, the findings increasing the probability of cirrhosis the most are dilated abdominal wall veins (LR = 9.5), encephalopathy (irrational behavior, disordered consciousness, and asterixis; LR = 8.8), reduced body or pubic hair (LR = 8.8), gynecomastia (LR = 7), ascites (LR = 6.6), spider angiomas (LR = 4.5), palmar erythema (LR = 4.3), jaundice (LR = 3.8), and peripheral edema (LR = 3). Other findings (but less compelling ones) are a liver edge that is firm to palpation (LR = 2.7), a palpable left lobe of the liver in the epigastrium (LR = 2.7), and splenomegaly (LR = 2.5). The only findings decreasing the probability of cirrhosis in these patients are absence of a palpable liver in the epigastrium (LR = 0.3) and absence of a firm liver edge (LR = 0.4).
CHAPTER 7 — JAUNDICE 67
EBM BOX 7-1
Findings Predicting Hepatocellular Disease in Patients with Jaundice* Finding (Reference)†
Sensitivity (%)
Specificity (%)
General Appearance Weight loss25,27
10-49
Skin Spider angiomas25,27 Palmar erythema25 Dilated abdominal veins25 abdomen
Ascites25 Palpable spleen25,27 Palpable gallbladder25 Palpable liver25,27 Liver tenderness25,27
Likelihood Ratio‡ if Finding Is Present
Absent
21-97
NS
NS
35-47 49 42
88-97 95 98
4.7 9.8 17.5
0.6 0.5 0.6
44 29-47 0† 71-83 37-38
90 83-90 69 15-17 70-78
4.4 2.9 0.04 NS NS
0.6 0.7 1.4 NS NS
*Diagnostic standard: For nonobstructive (vs. obstructive) jaundice, needle biopsy of liver, surgical exploration, or autopsy. †None of the 41 patients with medical jaundice in this study had a palpable gallbladder; for calculation of the LRs, 0.5 was added to all cells of the 2×2 table. ‡Likelihood ratio (LR) if finding present = positive LR; LR if finding absent = negative LR. NS, not significant. Click here to access calculator. HEPATOCELLULAR JAUNDICE Probability Decrease Increase –45% –30% –15% +15% +30% +45% LRs
0.1
Palpable gallbladder
0.2
0.5
1
2
5
10
LRs
Dilated abdominal veins Palmar erythema Spider angiomata Ascites Palpable spleen
D. DETECTING LARGE GASTROESOPHAGEAL VARICES IN PATIENTS WITH CIRRHOSIS In studies of more than 700 patients with cirrhosis who have not had prior gastrointestinal bleeding, no physical finding reliably predicts which patients have significant gastroesophageal varices (as detected by endoscopy). For most findings—caput medusae, spider angiomas, jaundice, hepatomegaly, splenomegaly, and hepatic encephalopathy—the LR is not
68 PART 3 — GENERAL APPEARANCE OF THE PATIENT
EBM BOX 7-2
Findings Predicting Cirrhosis in Patients with Chronic Liver Disease* Finding (Reference)† Skin Spider angiomas6,28–38 Palmar erythema29,31,32,34,37 Gynecomastia29,37 Reduction of body or pubic hair29,37 Jaundice 29,33,35,37,39 Dilated abdominal wall veins29,34,37 Abdomen Hepatomegaly29,32–36,38,40 Palpable liver in epigastrium35,38 Liver edge firm to palpation32,40 Splenomegaly28,30–36,38–40 Ascites28,29,31,33–35,39
Sensitivity (%)
Specificity (%)
33-84 12-70
Present
Absent
48-98 49-98
4.5 4.3
0.5 0.6
18-58 24-51
92-97 94-97
7 8.8
NS NS
16-44 9-51
83-99 79-100
3.8 9.5
0.8 NS
31-96
20-96
2.3
0.6
50-86
68-88
2.7
0.3
71-78
71-74
2.7
0.4
35-100
2.5
0.8
14-52
82-99
6.6
0.8
24-56 9-29
87-92 98-99
3.0 8.8
0.7 NS
5-85
Other Findings Peripheral edema29,33,34 Encephalopathy28,29,31
Likelihood Ratio‡ if Finding Is
*Diagnostic standard: For cirrhosis, needle biopsy of liver. †Definition of findings: For hepatomegaly and splenomegaly, examining clinician’s impression using palpation, percussion, or both; encephalopathy, disordered consciousness and asterixis.15 ‡Likelihood ratio (LR) if finding present = positive LR; LR if finding absent = negative LR. NS, not significant. Click here to access calculator.
CIRRHOSIS Probability Decrease Increase – 45% –30% –15% +15% +30% +45% LRs
0.1
0.2
0.5
Liver not palpable in epigastrium Liver edge not firm to palpation
1
2
5
10
LRs
Dilated abdominal wall veins Encephalopathy Diminished body or pubic hair Gynecomastia Ascites Spider angiomata or palmar erythema
CHAPTER 7 — JAUNDICE 69
EBM BOX 7-3
Findings Detecting Hepatopulmonary Syndrome in Patients with Chronic Liver Disease* Finding (Reference)
Sensitivity (%)
Specificity (%)
Clubbing45–48 Cyanosis45,46 Palmar erythema45,49 Spider angiomas45–49 Ascites47,48
22-80 8-86 57-80 39-97 56-79
64-95 79-99 54-70 26-70 20-57
Likelihood Ratio† if Finding Is Present
Absent
4.6 4.3 NS 1.4 NS
0.6 NS NS NS NS
*Diagnostic standard: For hepatopulmonary syndrome, all three of the following criteria were present: (1) cirrhosis, (2) contrast echocardiography revealing intrapulmonary right→left shunting, and (3) hypoxemia, variably defined as arterial pO2 <70 mm Hg49 or <80 mm Hg,45 alveolar-arterial pO2 gradient ≥15 mm Hg48 or >20 mm Hg,46 or either pO2 <70 mm Hg or AapO2 >20 mm Hg.47 †Likelihood ratio (LR) if finding present = positive LR; LR if finding absent = negative LR. NS, not significant. Click here to access calculator. HEPATOPULMONARY SYNDROME Probability Decrease Increase –45% –30% –15% +15% +30% +45% LRs
0.1
0.2
0.5
1
2
5
10
LRs
Clubbing Cyanosis
significant; only for ascites is the LR statistically significant (LR = 1.5), although its clinical significance is minimal.41-44 E. DETECTING HEPATOPULMONARY SYNDROME Hepatopulmonary syndrome is a serious complication of cirrhosis causing intrapulmonary vascular shunting and significant hypoxemia. In five studies of over 400 patients with cirrhosis (EBM Box 7-3), most awaiting liver transplantation, the findings of finger clubbing (LR = 4.6) and cyanosis (LR = 4.3) increased the probability of hepatopulmonary syndrome. The references for this chapter can be found on www.expertconsult.com.